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This study presents the clinical experiences of the New York Proton Center in employing proton pencil beam scanning (PBS) for the treatment of lung stereotactic body radiation therapy. It encompasses a comprehensive examination of multiple facets, including patient simulation, delineation of target volumes and organs at risk, treatment planning, plan evaluation, quality assurance, and motion management strategies. By sharing the approaches of the New York Proton Center and providing recommendations across simulation, treatment planning, and treatment delivery, it is anticipated that the valuable experience will be provided to a broader proton therapy community, serving as a useful reference for future clinical practice and research endeavors in the field of stereotactic body proton therapy for lung tumors. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic body proton therapy (SBPT) is an emerging treatment strategy for lung tumors that aims to combine the excellent local control benefits of ultra-hypofractionation with the physical advantages of protons, which reduce the integral dose to organs at risk (OARs) compared to photons. To date, however, very little data delivering SBPT in 5 or fewer fractions to lung tumors have been reported. Given that photon stereotactic body radiation therapy can struggle to deliver ablative doses to high-risk tumors (i.e., central/ultra-central location, prior in-field radiation, tumor size >5 cm, or the presence of severe pulmonary comorbidities) while adhering to OAR dose constraints, we hypothesized that SBPT would be an effective alternative for patients with high-risk tumors. Methods and Materials: Twenty-seven high-risk patients with 29 lung tumors treated with SBPT at the New York Proton Center between December 2019 and November 2022 were retrospectively identified. Patients were divided into three major subgroups: early-stage non-small cell lung cancer (NSCLC), locally recurrent NSCLC, and metastatic cancer from lung cancer or other histologies. Patient characteristics were reported using descriptive statistics, actuarial methods were used to quantify disease control rates, and toxicities were scored using CTCAE v 5.0. Results: The most common high-risk indications for SBPT were central/ultra-central tumor location (69.0%), severe COPD (48.1%), reirradiation (44.4%), significant pulmonary fibrosis (22.2%), and large tumor size > 5 cm (18.5%). In total, 96.6% of tumors were fully covered by the prescription dose without compromising target coverage. Three-year actuarial rates of local control for early-stage NSCLC, locally recurrent NSCLC, and metastatic patients were 89%, 100%, and 43%, respectively. Three-year actuarial rates of regional control were 89%, 67%, and 86%. Three-year actuarial rates of distant metastasis-free survival were 79%, 100%, and 0%. Two patients (7.4%), both of whom had clinically significant baseline interstitial lung disease and pre-treatment continuous oxygen demand, experienced grade =2 pulmonary toxicity (1 grade 3, 1 grade 5). There were no acute or late grade =2 toxicities related to esophagitis, cardiac injury, airway injury, pulmonary fibrosis, bronchopulmonary hemorrhage or brachial plexopathy. Conclusions: In the largest study of proton SBRT reported to date, SBPT has a favorable toxicity profile while being an effective approach for treating most high-risk tumors without requiring dose de-escalation or compromising tumor coverage and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: We investigate the impact of gender, race, and socioeconomic status on the diagnosis and management of bladder cancer in the United States. Methods: We utilized the National Cancer Database to stratify cases of urothelial cell carcinoma of the bladder as early (Tis, Ta, T1), muscle invasive (T2–T3, N0), locally advanced (T4, N1–3), and metastatic. Multivariate binomial and multinomial logistic regression analyses identified demographic characteristics associated with stage at diagnosis and receipt of cancer‐directed therapies. Odds ratios (OR) are reported with 95% confidence intervals. Results: After exclusions, we identified 331,714 early, 72,154 muscle invasive, 15,579 locally advanced, and 15,161 metastatic cases from 2004–2016. Relative to diagnosis at early stage, the strongest independent predictors of diagnosis at muscle invasive, locally advanced, and metastatic disease included Black race (OR = 1.19 [1.15–1.23], OR = 1.49 [1.40–1.59], OR = 1.66 [1.56–1.76], respectively), female gender (OR = 1.21 [1.18–1.21], OR = 1.16 [1.12–1.20], and OR = 1.34 [1.29–1.38], respectively), and uninsured status (OR = 1.22 [1.15–1.29], OR = 2.09 [1.94–2.25], OR = 2.57 [2.39–2.75], respectively). Additional demographic factors associated with delayed diagnosis included older age, treatment at an academic center, Medicaid insurance and patients from lower income/less educated/more rural areas (all p < 0.01). Treatment at a non‐academic center, older age, women, Hispanic and Black patients, lower income and rural areas were all less likely to receive cancer‐directed therapies in early stage disease (all p < 0.01). Women, older patients, and Black patients remained less likely to receive treatment in muscle invasive, locally advanced, and metastatic disease (all p < 0.01). Conclusion: Black race was the strongest independent predictor of delayed diagnosis and substandard treatment of bladder cancer. [ABSTRACT FROM AUTHOR]

Purposes: To evaluate the plan quality and robustness of both dose and dose rate of proton pencil beam scanning (PBS) transmission FLASH delivery in lung cancer treatment. Methods and materials: An in-house FLASH planning platform was used to optimize 10 lung cancer patients previously consecutively treated with proton stereotactic body radiation therapy (SBRT) to receive 3 and 5 transmission beams (Trx-3fds and Trx-5fds, respectively) to 34 Gy in a single fraction. Perturbation scenarios (n=12) for setup and range uncertainties (5 mm and 3.5%) were introduced, and dose-volume histogram and dose-rate-volume histogram bands were generated. Conventional proton SBRT clinical plans were used as a reference. RTOG 0915 dose metrics and 40 Gy/s dose rate coverage (V40Gy/s) were used to assess the dose and dose rate robustness. Results: Trx-5fds yields a comparable iCTV D2% of 105.3%, whereas Trx-3fds resulted in inferior D2% of 111.9% to the clinical SBRT plans with D2% of 105.6% (p<0.05). Both Trx-5fds and Trx-3fds plans had slightly worse dose metrics to organs at risk than SBRT plans. Trx-5fds achieved superior dosimetry robustness for iCTV, esophagus, and spinal cord doses than both Trx-3fds and conventional SBRT plans. There was no significant difference in dose rate robustness for V40Gy/s coverage between Trx-3fds and Trx-5fds. Dose rate distribution has similar distributions to the dose when perturbation exists. Conclusion: Transmission plans yield overall modestly inferior plan quality compared to the conventional proton SBRT plans but provide improved robustness and the potential for a toxicity-sparing FLASH effect. By using more beams (5-versus 3-field), both dose and dose rate robustness for transmission plans can be achieved. [ABSTRACT FROM AUTHOR]

Purpose: Experimental measurements of two‐dimensional (2D) dose rate distributions in proton pencil beam scanning (PBS) FLASH radiation therapy (RT) are currently lacking. In this study, we characterize a newly designed 2D strip‐segmented ionization chamber array (SICA) with high spatial and temporal resolution and demonstrate its applications in a modern proton PBS delivery system at both conventional and ultrahigh dose rates. Methods: A dedicated research beamline of the Varian ProBeam system was employed to deliver a 250‐MeV proton PBS beam with nozzle currents up to 215 nA. In the research and clinical beamlines, the spatial, temporal, and dosimetric performances of the SICA were characterized and compared with measurements using parallel‐plate ion chambers (IBA PPC05 and PTW Advanced Markus chamber), a 2D scintillator camera (IBA Lynx), Gafchromic films (EBT‐XD), and a Faraday cup. A novel reconstruction approach was proposed to enable the measurement of 2D dose and dose rate distributions using such a strip‐type detector. Results: The SICA demonstrated a position accuracy of 0.12 ± 0.02 mm at a 20‐kHz sampling rate (50 μs per event) and a linearity of R2 > 0.99 for both dose and dose rate with nozzle beam currents ranging from 1 to 215 nA. The 2D dose comparison to the film measurement resulted in a gamma passing rate of 99.8% (2 mm/2%). A measurement‐based proton PBS 2D FLASH dose rate distribution was compared to simulation results and showed a gamma passing rate of 97.3% (2 mm/2%). Conclusions: The newly designed SICA demonstrated excellent spatial, temporal, and dosimetric performances and is well suited for commissioning, quality assurance, and a wide range of clinical applications in proton PBS clinical and FLASH‐RT. [ABSTRACT FROM AUTHOR]

This study aimed to investigate a dose rate optimization framework based on the spot-scanning patterns to improve ultrahigh-dose-rate coverage of critical organs at risk (OARs) for proton pencil beam scanning (PBS) FLASH radiation therapy (ultrahigh dose-rate (often referred to as >40 Gy per second) delivery) and present implementation of a genetic algorithm (GA) method for spot sequence optimization to achieve PBS FLASH dose rate optimization under relatively low nozzle beam currents. First, a multifield FLASH plan was developed to meet all the dosimetric goals and optimal FLASH dose rate coverage by considering the deliverable minimum monitor unit constraint. Then, a GA method was implemented into the in-house treatment platform to maximize the dose rate by exploring the best spot delivery sequence. A phantom study was performed to evaluate the effectiveness of the dose rate optimization. Then, 10 consecutive plans for patients with lung cancer previously treated using PBS intensity-modulated proton therapy were optimized using 45 GyRBE in 3 fractions for both transmission and Bragg peak FLASH radiation therapy for further validation. The spot delivery sequence of each treatment field was optimized using this GA. The ultrahigh-dose-rate–volume histogram and dose rate coverage V 40GyRBE/s were investigated to assess the efficacy of dose rate optimization quantitatively. Using a relatively low monitor unit/spot of 150, corresponding to a nozzle beam current of 65 nA, the FLASH dose rate ratio V 40GyRBE/s of the OAR contour of the core was increased from 0% to ∼60% in the phantom study. In the patients with lung cancer, the ultrahigh-dose-rate coverage V 40GyRBE/s was improved from 15.2%, 15.5%, 17.6%, and 16.0% before the delivery sequence optimization to 31.8%, 43.5%, 47.6%, and 30.5% after delivery sequence optimization in the lungs-GTV (gross tumor volume), spinal cord, esophagus, and heart (for all, P <.001). When the beam current increased to 130 nA, V 40GyRBE/s was improved from 45.1%, 47.1%, 51.2%, and 51.4% to 65.3%, 83.5%, 88.1%, and 69.4% (P <.05). The averaged V 40GyRBE/s for the target and OARs increased from 12.9% to 41.6% and 46.3% to 77.5% for 65 and 130 nA, respectively, showing significant improvements based on a clinical proton system. After optimizing the dose rate for the Bragg peak FLASH technique with a beam current of 340 nA, the V 40GyRBE/s values for the lung GTV, spinal cord, esophagus, and heart were increased by 8.9%, 15.8%, 22%, and 20.8%, respectively. An optimal plan quality can be maintained as the spot delivery sequence optimization is a separate independent process after the plan optimization. Both the phantom and patient results demonstrated that novel spot delivery sequence optimization can effectively improve the ultrahigh-dose-rate coverage for critical OARs, which can potentially be applied in clinical practice for better OARs-sparing efficacy. [ABSTRACT FROM AUTHOR]

The National Association for Proton Therapy conducted 8 surveys of all operational United States proton centers (2012-2021) and analyzed the patients treated, diagnoses, and treatment complexity to evaluate trends and diversification of patients receiving proton therapy. Detailed surveys were sent in 2015, which requested data from 2012 to 2014, and then annually thereafter to active proton centers in the United States. The numbers of patient treated at each center for the preceding calendar year(s) were collated for tumors in the following categories: central nervous system, intraocular, pituitary, skull base/skeleton, head/neck, lung, retroperitoneal/soft tissue sarcoma, pediatric (solid tumors in children of age ≤18), gastrointestinal tract, urinary tract, female pelvic, prostate, breast, and "other." Complexity levels were assessed using Current Procedural Terminology codes 77520-77525. Survey response rates were excellent (100% in 2015 to 94.9% in 2021); additional publicly available information provided near-complete information on all centers. Trend comparisons between 2012 and 2021 showed that the total annual number of patients treated with protons gradually increased from 5377 to 15,829. The largest numeric increases were for head/neck (316 to 2303; 7.3-fold), breast (93 to 1452; 15.6-fold), and gastrointestinal tumors (170 to 1259; 7.4-fold). Patient numbers also increased significantly for central nervous system (598 to 1743; 2.9-fold), pediatric (685 to 1870; 2.7-fold), and skull base tumors (179 to 514; 2.9-fold). For prostate cancer, the percentage of proton-treated patients decreased from 43.4% to 25.0% of the total. Simple compensated treatments decreased from 43% in 2012 to 7% in 2021, whereas intermediate complexity treatments increased from 45% to 73%. The number of patients treated with protons is gradually increasing, with a substantial proportionate decline in patients with prostate cancer receiving proton therapy. The number of patients treated for "commonly accepted" indications for protons (eg, pediatric, central nervous system, and skull base tumors) is gradually increasing. Greater proportional increases were observed for breast, lung, head/neck, and gastrointestinal tumors. Treatment complexity is gradually increasing over time. [ABSTRACT FROM AUTHOR]

HER2-positive (HER2+) breast cancer historically exhibited the most adverse local outcomes and, consequently, has had limited representation among trials of partial breast irradiation (PBI). We hypothesized that with contemporary HER2-targeted agents, patients may now exhibit excellent disease control outcomes after adjuvant PBI. Using a prospectively maintained institutional database, we identified patients with HER2+ breast cancer treated with breast conserving surgery (BCS) and PBI from 2000 to 2022. Salient clinicopathologic and treatment parameters were collected. All patients received external beam PBI to 40 Gy in 10 daily fractions. Cumulative incidence functions were calculated to estimate the incidence of local recurrence (LR) with the competing risk of death. We identified 1248 patients who underwent PBI at our institution, of whom the study cohort comprised 52 (4%) with HER2+ breast cancer (median age, 64 years; range, 44-87). Nearly all had T1 tumors (98%; median size, 12 mm [range, 1-21 mm]). Most had estrogen receptor positive disease (88%), and all patients had negative surgical margins. Nearly all underwent sentinel node biopsy (94%), with the remainder undergoing no surgical axillary evaluation. Forty-two (81%) received chemotherapy; 40 (77%), hormone therapy; and 42 (81%), HER2-directed therapy, most commonly trastuzumab. At 143.8 person-years of follow-up (range, 7-226 months for each patient), we observed 2 LR events at 14 and 26 months, respectively, yielding a 2-year LR rate of 3.8%. No regional or distant recurrences were observed, nor were any breast-specific mortality events. Two deaths were observed, both without evidence of disease. Among a cohort of patients with HER2+ early-stage breast cancer managed with BCS and PBI, we observed a 2-year LR rate of 3.8%, with no regional or distant recurrences and excellent overall survival. These findings require confirmation with longer follow-up among larger cohorts but appear consistent with the excellent results of contemporary randomized trials of PBI unselected for HER2 status. [ABSTRACT FROM AUTHOR]

Purpose: Ultrahigh dose-rate FLASH radiation therapy has emerged as a modality that promises to reduce normal tissue toxicity while maintaining tumor control. Previous studies of gastrointestinal toxicity using passively scattered FLASH proton therapy (PRT) have, however, yielded mixed results, suggesting that the requirements for gastrointestinal sparing by FLASH are an open question. Furthermore, the more clinically relevant pencil beam scanned (PBS) FLASH PRT has not yet been assessed in this context, despite differences in the spatiotemporal dose-rate distributions compared with passively scattered PRT. Here, to our knowledge, we provide the first report on the effects of PBS FLASH PRT on acute gastrointestinal injury in mice after whole abdominal irradiation., Methods and Materials: Whole abdominal irradiation was performed on C57BL/6J mice using the entrance channel of the Bragg curve of a 250 MeV PBS proton beam at field-averaged dose rates of 0.6 Gy/s for conventional (CONV) and 80 to 100 Gy/s for FLASH PRT. A 2D strip ionization chamber array was used to measure the dose and dose rate for each mouse. Survival was assessed at 14 Gy. Intestines were harvested and processed as Swiss rolls for analysis using a novel artificial intelligence-based crypt assay to quantify crypt regeneration 4 days after irradiation., Results: Survival was significantly reduced after 14 Gy FLASH PRT compared with CONV (P < .001). Our artificial intelligence-based crypt assays demonstrated no significant difference in intestinal crypts/cm or crypt depth between groups 4 days after irradiation. Furthermore, we found no significant difference in 5-ethynyl-2'-deoxyuridine + cells/crypt or Olfactomedin4 + intestinal stem cells with FLASH relative to CONV PRT., Conclusions: Overall, our data demonstrate significantly impaired survival after abdominal PBS FLASH PRT without apparent differences in intestinal histology 4 days after irradiation., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To provide a comprehensive assessment of various fractionation schemes in radiation therapy for breast cancer, with a focus on side effects, cosmesis, quality of life, risks of recurrence, and survival outcomes., Design: Systematic review and meta-analysis., Data Sources: Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (from inception to 23 October 2023)., Study Selection: Included studies were randomised controlled trials focusing on conventional fractionation (CF; daily fractions of 1.8-2 Gy, reaching a total dose of 50-50.4 Gy over 5-6 weeks), moderate hypofractionation (MHF; fraction sizes of 2.65-3.3 Gy for 13-16 fractions over 3-5 weeks), and/or ultra-hypofractionation (UHF; schedule of only 5 fractions)., Data Extraction: Two independent investigators screened studies and extracted data. Risk of bias and quality of evidence were assessed using the Cochrane Collaboration's tool and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach, respectively., Data Synthesis: Pooled risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random effects model. Heterogeneity was analysed using Cochran's Q test and I 2 statistic. Network meta-analysis was used to integrate all available evidence., Main Outcome Measures: The pre-specified primary outcome was grade ≥2 acute radiation dermatitis and late radiation therapy related side effects; secondary outcomes included cosmesis, quality of life, recurrence, and survival metrics., Results: From 1754 studies, 59 articles representing 35 trials (20 237 patients) were assessed; 21.6% of outcomes showed low risk of bias, whereas 78.4% had some concerns or high risk, particularly in outcome measurement (47.4%). The RR for grade ≥2 acute radiation dermatitis for MHF compared with CF was 0.54 (95% CI 0.49 to 0.61; P<0.001) and 0.68 (0.49 to 0.93; P=0.02) following breast conserving therapy and mastectomy, respectively. Hyperpigmentation and grade ≥2 breast shrinkage were less frequent after MHF than after CF, with RRs of 0.77 (0.62 to 0.95; P=0.02) and 0.92 (0.85 to 0.99; P=0.03), respectively, in the combined breast conserving therapy and mastectomy population. However, in the breast conserving therapy only trials, these differences in hyperpigmentation (RR 0.79, 0.60 to 1.03; P=0.08) and breast shrinkage (0.94, 0.83 to 1.07; P=0.35) were not statistically significant. The RR for grade ≥2 acute radiation dermatitis for UHF compared with MHF was 0.85 (0.47 to 1.55; P=0.60) for breast conserving therapy and mastectomy patients combined. MHF was associated with improved cosmesis and quality of life compared with CF, whereas data on UHF were less conclusive. Survival and recurrence outcomes were similar between UHF, MHF, and CF., Conclusions: MHF shows improved safety profile, cosmesis, and quality of life compared with CF while maintaining equivalent oncological outcomes. Fewer randomised controlled trials have compared UHF with other fractionation schedules, but its safety and oncological effectiveness seem to be similar with short term follow-up. Given the advantages of reduced treatment time, enhanced convenience for patients, and potential cost effectiveness, MHF and UHF should be considered as preferred options over CF in appropriate clinical settings, with further research needed to solidify these findings., Systematic Review Registration: PROSPERO CRD42023460249., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; IC has received consulting fees from Pfizer, Novartis, Eli Lilly, Seagen, Gilead, Astra Zeneca, Daiichi Sankyo, and Menarini StemLine and is a clinical board member of the European Society for Radiotherapy and Oncology (unpaid); JQC has received funding from the Canadian Institutes of Health Research and honorariums from Roche, Pfizer, Novartis, AstraZeneca, Well Doc Alberta, Merck, La Roche-Posay, Knight, Seagen, Oncology Education, and Gilead; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Currently, there are no data regarding the impact of treatment interruptions during radiotherapy for breast cancer. In this study, we examine the correlation between treatment interruptions during radiotherapy and outcomes in triple-negative breast cancer patients., Methods: A total of 35 845 patients with triple-negative breast cancer treated between 2010 and 2014 were identified and analyzed from the National Cancer Database. The number of interrupted radiotherapy treatment days was calculated as the difference between the total elapsed days from the start to end of radiation treatment (both initial treatment and boost treatment, when boost was administered) and the total number of expected treatment days, defined as the number of expected treatment days with an addition of 2 weekend days for every multiple of 5 treatment days. Binomial multivariate regression analysis was used to detect correlates of treatment interruptions, and propensity-score matched multivariable Cox proportional hazard models were used to evaluate the association between treatment interruption and overall survival (OS)., Results: When modeled as a continuous variable, longer treatment duration was associated with poorer OS (hazard ratio [HR] = 1.023, 95% confidence interval [CI] = 1.015 to 1.031). In reference to 0-1 days of interruption, patients with 2-5 interrupted days (HR = 1.069, 95% CI = 1.002 to 1.140 interrupted days), 6-10 interrupted days (HR = 1.239, 95% CI = 1.140 to 1.348 interrupted days), and 11-15 interrupted days (HR = 1.265, 95% CI = 1.126 to 1.431 interrupted days) experienced increasing likelihood of mortality., Conclusion: In the first study of its kind, we report a correlation between treatment interruptions during adjuvant radiotherapy in triple-negative breast cancer and OS., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Recurrent or new primary breast cancer requiring comprehensive regional nodal irradiation after prior radiation therapy (RT) to the supraclavicular area and upper axilla is challenging due to cumulative brachial plexus (BP) dose tolerance. We assessed BP dose sparing achieved with pencil beam scanning proton therapy (PBS-PT) and photon volumetric modulated arc therapy (VMAT)., Methods and Materials: In an institutional review board-approved planning study, all patients with ipsilateral recurrent breast cancer treated with PBS-PT re-RT (PBT1) with at least partial BP overlap from prior photon RT were identified. Comparative VMAT plans (XRT1) using matched BP dose constraints were developed. A second pair of proton (PBT2) and VMAT (XRT2) plans using standardized target volumes were created, applying uniform prescription dose of 50.4 per 1.8 Gy and a maximum BP constraint <25 Gy. Incidence of brachial plexopathy was also assessed., Results: Ten consecutive patients were identified. Median time between RT courses was 48 months (15-276). Median first, second, and cumulative RT doses were 50.4 Gy (range, 42.6-60.0), 50.4 Gy relative biologic effectiveness (RBE) (45.0-64.4), and 102.4 Gy (RBE) (95.0-120.0), respectively. Median follow-up was 15 months (5-33) and 18 months for living patients (11-33) Mean BP max was 37.5 Gy (RBE) for PBT1 and 36.9 Gy for XRT1. Target volume coverage of V85% (volume receiving 85% of prescription dose), V90%, and V95% were numerically lower for XRT1 versus PBT1. Similarly, axilla I-III and supraclavicular area coverage were significantly higher for PBT2 than XRT2 at dose levels of V55%, V65%, V75%, V85%, and V95%. Only axilla I V55% did not reach significance ( P = .06) favoring PBS-PT. Two patients with high cumulative BPmax (95.2 Gy [RBE], 101.6 Gy [RBE]) developed brachial plexopathy symptoms with ulnar nerve distribution neuropathy without pain or weakness (1 of 2 had symptom resolution after 6 months without intervention)., Conclusions: PBS-PT improved BP sparing and target volume coverage versus VMAT. For patients requiring comprehensive re-RT for high-risk, nonmetastatic breast cancer recurrence with BP overlap and reasonable expectation for prolonged life expectancy, PBT may be the preferred treatment modality., Competing Interests: J. Isabelle Choi reports personal fees from Varian Medical Systems outside of the scope of this work., (© 2023 The Author(s).)

This study presents the clinical experiences of the New York Proton Center in employing proton pencil beam scanning (PBS) for the treatment of lung stereotactic body radiation therapy. It encompasses a comprehensive examination of multiple facets, including patient simulation, delineation of target volumes and organs at risk, treatment planning, plan evaluation, quality assurance, and motion management strategies. By sharing the approaches of the New York Proton Center and providing recommendations across simulation, treatment planning, and treatment delivery, it is anticipated that the valuable experience will be provided to a broader proton therapy community, serving as a useful reference for future clinical practice and research endeavors in the field of stereotactic body proton therapy for lung tumors., Competing Interests: Authors’ disclosure of potential conflicts of interest Drs. Lin, Choi, and Simone have received honoraria from Varian Medical Systems, which are outside the scope of this work. Dr. Kang has received a Varian research grant unrelated to this study., (© 2023 Old City Publishing, Inc.)

Purpose: Phantosmia, an underreported toxicity of brain radiation therapy (RT), is defined as an olfactory disorder resulting in a malodorous phantom smell. This study aimed to characterize the incidence of phantosmia in patients treated with intensity modulated proton therapy (IMPT)., Methods and Materials: In this institutional review board-approved retrospective study, the electronic medical record of a pencil beam scanning-only proton center was queried for patients ≤39 years of age who received IMPT for primary intracranial, metastatic intracranial, skull base, nasopharyngeal or sinonasal neoplasms between August 2019 and December 2020. Patient, clinical, and phantosmia-related characteristics were collected. The olfactory region was defined to include the olfactory bulb and tract. Phantosmia severity was graded by intervention use (mild, no intervention; moderate, supportive treatment; severe, RT discontinuation)., Results: Ninety-nine patients met the inclusion criteria. Twelve patients (12.1%) reported phantosmia. Patients described perceiving a "chlorine," "broccoli," "stale water," "metallic," or "noxious" smell. Of the patients who reported phantosmia, median age was 17 (12-33) years, 66.7% were male, and 91.7% had intracranial tumors. None of the patients had prior RT. Chemoradiotherapy treatment did not correlate with phantosmia development (odds ratio, 1.09; 95% confidence interval, 0.32-3.70; P  = .90). Ten patients experienced accompanying toxicities, including taste changes (n = 3), vision disturbances (n = 5), and nausea/emesis (n = 7). Phantosmia was mild (n = 7) or moderate (n = 5). All patients completed their RT course. Sixty-seven percent received craniospinal irradiation (CSI) while 33% received focal brain RT, with the olfactory region receiving doses as low as 0.5 Gy. Notably, 8 of 27 patients who received CSI (30%) reported phantosmia (odds ratio, 7.66; 95% confidence interval, 2.07-28.34; P  = .002)., Conclusions: In the first-ever study examining radiation-induced phantosmia among children and young adults treated with IMPT, all affected patients received irradiation dose to the olfactory region. Physician awareness of phantosmia, especially in the context of CSI, may improve the patient experience and treatment compliance. A prospective study is needed to elucidate frequency, severity, and phantosmia mechanism., (© 2021 Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.)

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.